There is evidence for the involvement of membrane-bound receptor and enzyme systems in the biological effects of ethanol. It is also widely assumed that ethanol or adaptive changes to ethanol consumption do not affect membrane proteins directly, but rather influence their activity indirectly through actions on membrane lipids and changes in membrane fluidity. One might expect then that interactions between different membrane-proteins would be particularly sensitive to ethanol. We have long been interested in the mechanism of interaction between calcium-linked alpha- and cyclic AMP-linked beta-adrenergic receptors. We have shown that in vitro incubation of isolated rat liver cells in a serum-free medium leads to a rapid conversion of the adrenergic activation of glycogen phosphorylase from an alpha-l to a beta-receptor mediated event. This conversion reflects inverse, reciprocal changes in the coupling of the two receptors to their respective post-receptor pathways, and requires protein synthesis. Activation of membrane phospholipase A2 and protein kinase C are also involved in the conversion response. Studies in progress are aimed to further clarify the nature of the phospholipase and protein involvement. We will also determine whether in vitro or in vivo treatment with ethanol would influence the time-dependent change in adrenergic receptor phenotype in isolated rat liver cells. These studies could add to our understanding of how ethanol influences adaptive changes in neurotransmitter receptor function.